Herpes simplex virus (HSV) ocular infection is the leading non-traumatic cause of blindness in the United States. The major morbidity results from viral reactivation in ganglia and recurrent ocular shedding of HSV. Our long-term objective is to develop an understanding of reactivation of a latent infection and the interactions between reactivation and ocular shedding. Such an understanding would ultimately aid in reducing the morbidity of recurrent ocular disease. To study reactivation and shedding, we use a mouse model. BALB/c mice are inoculated by the corneal route. At the latent stage, they are treated with epinephrine iontophoresis (EI) across the cornea. One of us has shown that this treatment induces ocular shedding in 70% of mice. Our first aim is to increase the versatility of this model by experiemental manipulations. these manipulations are designed to produce an increase in the degree of ocular shedding and to produce clinical disease at the cornea from recurrent shedding. Secondly, the model will be used to study the mechanics of reactiviation as it relates to ocular shedding. We will use the standard explant and homogenate cultures of ganglia as well as molecular techniques of DNA: DNA hybridization and in situ hybridization on tissue sections to detect HSV transcripts. Specific questions include the anatomic sites of latency and reactivation, the incidence of reactivation without shedding, the correlation between shedding and the amount of HSV DNA in ganglia, the effect of multiple shedding on HSV DNA in ganglia, and differences in the organization and/or transcription of HSV DNA in shedders and non-shedders. Thirdly, we will use the mouse model of EI to determine if prior immunization effects reactivation or shedding. Specifically, active and passive immunization will be compared in regards to the amount of HSV DNA in ganglia and the capacity of EI to induce reactiviation and shedding. These last experiments are clinically relevant since it is unlikely that a herpes vaccine will altogether eliminate ganglionic infection. Our mouse model will provide a test system to determine if any immunization program will reduce recurrent ocular shedding.